YARS1 encodes tyrosyl-tRNA synthetase 1, which primarily catalyzes the attachment of tyrosine to tRNA(Tyr) in protein synthesis 1. Beyond its canonical aminoacylation function, YARS1 exhibits several noncanonical activities that contribute to both normal physiology and disease pathogenesis. The protein functions as an actin-bundling factor, with this activity being enhanced by Charcot-Marie-Tooth (CMT) disease mutations, leading to actin cytoskeleton disorganization in neurons 2. YARS1 also acts as a positive regulator of poly-ADP-ribosylation in the nucleus, independently of its aminoacylation activity, with resveratrol binding promoting nuclear relocalization and PARP1 stimulation 1. Disease-causing mutations in YARS1 are associated with dominant CMT neuropathy and autosomal recessive multisystem disorders, with phenotypic diversity correlating with mutations affecting different functional domains 3. The recurrent p.(Arg367Trp) mutation causes a distinct neurodevelopmental phenotype including microcephaly, developmental delay, and multisystem involvement 3. In cancer contexts, YARS1 is upregulated and redirects tyrosine toward translation, particularly in hepatocellular carcinoma, where it supports tumor growth through tyrosine-dependent translation of key metabolic proteins 4. YARS1 expression correlates with poor prognosis in multiple cancer types and represents a potential therapeutic target 5.